Small Extracellular Vesicles Released from Bioglass/Hydrogel Scaffold Promote Vascularized Bone Regeneration by Transferring miR-23a-3p

Abstract

Background The treatment of critical-size bone defect is a great difficulty in orthopedics. Osteogenesis and angiogenesis are critical issue during the process of bone repair and remodeling. Mesenchymal stem cells (MSCs)-derived exosomes have the same therapeutic effect to MSCs-based therapies. The effect of human umbilical cord MSCs-derived sEVs (hUC-MSCs-sEVs) on vascularized bone regeneration and the potential mechanism remains to be investigated. Herein, we aimed to explore the therapeutic effect and the mechanism of hUC-MSCs-sEVs on critical-size bone defect. Methods To investigate the potential osteogenesis and angiogenesis effects of sEVs in vitro, we extracted sEVs from hUC-MSCs, and then sEVs were co-incubated with BMSCs and HUVECs. We next investigated the effect and potential mechanism of sEVs on the effects of osteogenesis and angiogenesis. We fabricated 3D-printed bioglass scaffold with Gelma/nanoclay hydrogel coatings to load sEVs (BG-gel-sEVs) to ensure in vivo sustained efficacy of sEVs. Finally, the skull defect model was used to evaluate the capacity of vascularized bone regeneration of the composited scaffolds. Results hUC-MSCs-sEVs facilitated calcium deposition and the endothelial network formation, inducing osteogenic differentiation and angiogenesis by delivering miR-23a-3p to activate PTEN/AKT signaling pathway. Additionally, the BG-gel-sEVs composited scaffold achieved vascularized bone regeneration in vivo. Conclusion This finding illuminated that hUC-MSCs-sEVs promoted osteogenesis and angiogenesis by delivering miR-23a-3p to activate PTEN/AKT signaling pathway, achieving vascularized bone regeneration.

Hypoxic Preconditional Engineering Small Extracellular Vesicles Promoted Intervertebral Disc Regeneration by Activating Mir‐7‐5p/NF‐Κb/Cxcl2 Axis

“…MicroRNA(miRNA) is instrumental in regulating gene expression by binding the 3′‐UTR or amino acid coding sequences of the target gene. [ 30 ] To further verify the underlying mechanism of anti‐inflammatory, proteoglycans synthesis and collagen formation mediated by HP‐sEVs, miRNA expression profiles of sEVs and HP‐sEVs were measured by high‐throughput small RNA sequencing. The count number distribution of the total small RNA of sEVs and HP‐sEVs was different ( Figure 5 a ).…”

Biomaterial‐Facilitated Local Delivery of Stem Cell‐Derived Small Extracellular Vesicles: Perspectives in Surgical Therapy

“…Hu et al used GelMA/nanoclay HG with a bioglass scaffold to transfer exosomal miR-23a-3p from UC MSCs for vascularized bone regeneration through the PTEN/Akt pathway. [38] Similarly, Zhang et al revealed that bone repair could be accelerated by enhancing angiogenesis mediated by exosomal miR-21 delivered locally by a HA HG with nanoHAp/poly-𝜖-caprolactone (PCL) scaffold. [39]…”

Efforts to promote osteogenesis–angiogenesis coupling for bone tissue engineering

“…The commonly used microspheres include liposome vectors, 92 organic carriers (such as polyethyleneimine (PEI), 93 chitosan (CS), 94 gelatin 95 ), inorganic material carriers (such as mesoporous silica nanoparticles (MSNs) 96,97 ), and exosomes. 98,99 Table 2 summarized the preparation of microspheres loaded with bioactive substances and their effect on vascular osteogenesis. The binding of microspheres loaded with bioactive substances on the scaffold surface mainly includes electrostatic adsorption and chemical binding.…”